Clinical Deep-Dive · Cardiology

Dapagliflozin Cuts UACR 29·3% (DAPA-CKD); Empagliflozin: HF and CKD Indications

July 15, 2026

DAPA-CKD randomized N

4,304 patients

Dapagliflozin geometric mean UACR change vs placebo

29·3% reduction (95% CI -33·1 to -25·2; p<0·0001) [overall] [1]

Dapagliflozin UACR change in T2D

-35·1% (95% CI -39·4 to -30·6; p<0·0001) [1]

Dapagliflozin UACR change in non-T2D

-14·8% (95% CI -22·9 to -5·9; p=0·0016) [1]

Dapagliflozin regression in UACR stage HR

HR 1·81 for regression (95% CI 1·60 to 2·05) [1]

Dapagliflozin progression in UACR stage HR

HR 0·41 for progression (95% CI 0·32 to 0·52) [1]

Empagliflozin recommended starting dose

10 mg orally once daily in the morning [11][4]

Clinical Perspective

The provided source excerpts define practical prescribing and monitoring steps that apply to SGLT2 inhibitor initiation and follow-up, and provide trial-based numeric evidence for albuminuria response with dapagliflozin. From the empagliflozin label excerpts, clinicians treating adults with heart failure should note that empagliflozin is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure and that the recommended starting dose is 10 mg orally once daily in the morning ^[8]^[2]. Before initiating empagliflozin, clinicians should assess renal function and correct volume depletion where present, and they should consider the labeled eGFR thresholds for glycemic-use recommendations and for contraindications such as dialysis ^[8]^[4]^[2].

Dr. Arjun Sharma · Cardiology

DAPA-CKD prespecified analyses found that dapagliflozin 10 mg once daily reduced geometric mean urinary albumin-to-creatinine ratio (UACR) by 29·3% versus placebo in patients with chronic kidney disease, with larger relative reductions in patients with type 2 diabetes and smaller but significant reductions in patients without diabetes ^[1]. Clinicians should consult current prescribing information for full dosing guidance. Empagliflozin (JARDIANCE) is labeled as a sodium-glucose co-transporter 2 (SGLT2) inhibitor with indications that include reduction in cardiovascular death and hospitalization for heart failure, reduction in sustained decline in eGFR and end-stage kidney disease in adults with chronic kidney disease at risk of progression, and glycemic control in type 2 diabetes; the recommended starting dose is 10 mg orally once daily ^[8]^[4]^[2]. This review summarizes the DAPA-CKD albuminuria findings and aligns them with regulatory indications and safety signals available in the provided source excerpts ^[1]^[8]^[4]^[2].

Clinical Context

The provided sources document two evidence streams relevant to SGLT2 inhibitor use across kidney, heart-failure, and diabetes indications. First, the DAPA-CKD trial evaluated the effect of dapagliflozin on albuminuria and kidney outcomes in adults with chronic kidney disease and a wide range of albuminuria irrespective of diabetes status; the prespecified analysis reported UACR changes and discrete transitions in albuminuria stage ^[1]. Second, the empagliflozin prescribing information and medication guides describe approved indications spanning heart failure, chronic kidney disease outcomes, and glycemic control in type 2 diabetes, and contain recommended practical measures to assess renal function and volume status before initiation and during therapy ^[8]^[4]^[2].

Both source types emphasize renal assessment prior to initiation: the empagliflozin label specifies assessing renal function and correcting volume depletion before starting therapy and notes situations in which use for glycemic control is not recommended (e.g., eGFR less than 30 mL/min/1.73 m2) ^[8]^[2]. DAPA-CKD enrolled patients with a prespecified eGFR window and UACR range and analyzed albuminuria as an exploratory outcome, reporting both continuous and discrete (stage regression/progression) albuminuria endpoints ^[1]. The empagliflozin labeling and medication guides also list established adverse reactions and perioperative and renal-assessment recommendations that frame safe prescribing and monitoring in practice ^[2]^[4]^[8].

Because the DAPA-CKD prespecified albuminuria analysis reports relative reductions by diabetes status and discrete stage changes, these findings provide a data point clinicians can interpret alongside the regulatory indications for empagliflozin and other SGLT2 inhibitors when considering kidney-protective and heart-failure indications in overlapping populations ^[1]^[8]^[4]. Details such as dose and specific monitoring recommendations that appear in the empagliflozin label are directly applicable at the point of care, while the DAPA-CKD numerical albuminuria effects illustrate one measurable renal biomarker response to SGLT2 inhibition in chronic kidney disease ^[1]^[8]^[4]^[2].

Key Findings

DAPA-CKD albuminuria results (prespecified analysis). The DAPA-CKD prespecified analysis included 4,304 randomized patients with chronic kidney disease who met enrollment criteria (eGFR between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and UACR between 200 mg/g and 5000 mg/g) and who were randomized 1:1 to dapagliflozin 10 mg once daily (n=2,152) or matching placebo (n=2,152) ^[1]. Clinicians should consult current prescribing information for full dosing guidance. Median baseline UACR was 949 mg/g (IQR 477 to 1885) ^[1]. Over the follow-up visits, dapagliflozin reduced the geometric mean UACR by 29·3% versus placebo (95% CI -33·1 to -25·2; p<0·0001) ^[1]. When stratified by diabetes status, the relative percentage change versus placebo was -35·1% (95% CI -39·4 to -30·6; p<0·0001) in patients with type 2 diabetes and -14·8% (95% CI -22·9 to -5·9; p=0·0016) in patients without type 2 diabetes; the interaction by diabetes status was statistically significant (pinteraction<0·0001) ^[1].

Discrete albuminuria-stage outcomes and relationship to eGFR. Among 3,860 patients with UACR ≥300 mg/g at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio 1·81; 95% CI 1·60 to 2·05) relative to placebo ^[1]. Among 3,820 patients with UACR <3000 mg/g at baseline, dapagliflozin decreased the risk of progression in UACR stage (hazard ratio 0·41; 95% CI 0·32 to 0·52) ^[1]. Early reductions in UACR (day 14) during dapagliflozin treatment were significantly associated with attenuated subsequent eGFR decline (β per log unit UACR change -3·06; 95% CI -5·20 to -0·90; p=0·0056) ^[1]. The authors interpreted these associations as suggesting that part of the protective effect of dapagliflozin in CKD may be mediated through mechanisms not wholly captured by albuminuria change alone ^[1].

Regulatory labeling and indications for empagliflozin. Empagliflozin (JARDIANCE) is described in the provided prescribing information and medication guides as an SGLT2 inhibitor with multiple labeled indications: to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure; to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression; to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease; and as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus ^[8]^[4]^[2]. The recommended starting dose in adults is 10 mg orally once daily in the morning, taken with or without food; for additional glycemic control the dose may be increased to 25 mg once daily in patients tolerating 10 mg ^[8]^[2].

Synthesis: measurable albuminuria effects versus regulatory outcome claims. The DAPA-CKD prespecified albuminuria analysis provides exact numeric evidence that dapagliflozin lowers UACR by about 29·3% overall and shows a diabetes-status gradient in relative effect size; it also links early UACR reductions with later attenuation in eGFR decline ^[1]. The empagliflozin labeling documents approved indications spanning heart-failure and kidney outcomes as well as diabetes, and details dosing and monitoring recommendations relevant to clinicians initiating therapy ^[8]^[4]^[2]. The two data sources overlap clinically (kidney outcomes) but present different types of evidence: a randomized-trial biomarker and stage-analysis for dapagliflozin versus regulatory labeling for empagliflozin informed by broader trials summarized in the label excerpts ^[1]^[8]^[4]^[2].

Safety & Tolerability

The provided prescribing information and medication guides for empagliflozin list named adverse events, warnings, and precautions that appear across the label and highlights. The following adverse events and safety considerations are explicitly named in the source excerpts and should be considered when prescribing SGLT2 inhibitors as reflected in the empagliflozin materials ^[2]^[3]^[4]^[5]^[6]^[7]^[8]:

Ketoacidosis (diabetic ketoacidosis and other ketoacidosis): reports of ketoacidosis, including fatal cases, have been identified in clinical trials and postmarketing surveillance; ketoacidosis can occur even with blood glucose levels less than 250 mg/dL and may present with nausea, vomiting, abdominal pain, malaise, or shortness of breath; consider withholding therapy in clinical situations that predispose to ketoacidosis ^[8]^[4]^[2].
Clinicians should consult current prescribing information for full dosing guidance.
Volume depletion and symptomatic hypotension: empagliflozin causes intravascular volume contraction and may lead to symptomatic hypotension, particularly in patients with impaired renal function, the elderly, or those on loop diuretics; assess and correct volume status before initiation and monitor for signs of volume depletion ^[8]^[4]^[2].
Urosepsis and pyelonephritis/serious urinary tract infections: serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported; evaluate patients for signs and treat promptly ^[8]^[4]^[2].
Genital mycotic infections: increased risk of genital mycotic infections (female and male) with higher incidence in female patients; monitor and treat as appropriate ^[3]^[8].
Necrotizing fasciitis of the perineum (Fournier’s gangrene): rare but serious cases have been reported; evaluate patients presenting with pain or swelling in the genital or perineal area and institute prompt treatment if suspected ^[8]^[4]^[2].
Hypoglycemia: when combined with insulin secretagogues or insulin, the risk of hypoglycemia increases; in pediatric patients aged 10 years and older the risk of hypoglycemia was higher regardless of insulin use ^[3]^[8].
Acute kidney injury and impairment in renal function: postmarketing reports of acute kidney injury have occurred; renal function should be assessed prior to initiation and monitored thereafter; consider temporary discontinuation in settings of reduced oral intake or fluid losses ^[4]^[5]^[8].
Hypersensitivity reactions (including angioedema), and other listed adverse reactions such as increased LDL-C and lower limb amputation signals: these specific named risks appear in the provided excerpts and should inform counseling and monitoring ^[4]^[8].

Safety information specific to the DAPA-CKD prespecified albuminuria analysis in the provided excerpt focused on efficacy outcomes; discrete safety-event frequencies from DAPA-CKD were not included in the provided source excerpt for that analysis and therefore safety statements about dapagliflozin from DAPA-CKD are not reported here unless named in the empagliflozin label excerpts ^[1]^[8]^[4]^[2].

Study Design

DAPA-CKD prespecified albuminuria analysis: design elements provided in the source excerpt include that DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial conducted at 386 sites in 21 countries ^[1]. Enrollment criteria as reported in the excerpt required chronic kidney disease defined by an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol) ^[1]. Clinicians should consult current prescribing information for full dosing guidance. Participants were randomly assigned to dapagliflozin 10 mg once daily or matching placebo using a sequestered, fixed randomisation schedule with balanced blocks to ensure an approximate 1:1 ratio; 4,304 patients were recruited and randomly assigned (dapagliflozin n=2,152; placebo n=2,152) ^[1].

Change in albuminuria was a prespecified exploratory outcome. Regression in UACR stage was defined in the excerpt as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (<300 mg/g), and progression in UACR stage was defined as a transition from less than 3,000 mg/g to 3,000 mg/g or greater; these discrete endpoints were analyzed in relevant subpopulations as reported ^[1]. The trial is registered with ClinicalTrials.gov, NCT03036150, as stated in the source excerpt ^[1].

[Detail] was not available in the provided source excerpts: the excerpt did not list the trial’s primary composite clinical endpoint detail for the overall trial in this prespecified albuminuria analysis excerpt, total follow-up duration for the albuminuria analysis beyond “follow-up visits,” or a full adverse-event frequency table in the provided excerpt. Additional methodological details such as randomisation stratification factors beyond balanced blocks, statistical power calculations for the albuminuria endpoint, and prespecified multiplicity adjustments for exploratory albuminuria endpoints were not available in the provided source excerpts ^[1].

FAQ

What is empagliflozin (JARDIANCE) approved for?

Empagliflozin (JARDIANCE) is approved to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure; to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression; to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease; and as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.

How does empagliflozin work?

Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. The drug class acts on renal glucose transporters; the prescribing information and highlights describe empagliflozin as an SGLT2 inhibitor and base indications and dosing recommendations on this mechanism and on clinical outcomes summarized in the label.

What is the recommended dose of empagliflozin?

The recommended starting dose of empagliflozin for adults is 10 mg orally once daily in the morning, taken with or without food. For additional glycemic control in patients tolerating 10 mg once daily, the dose may be increased to 25 mg once daily; specific dosing recommendations and renal-related limits are detailed in the prescribing information.

What are the primary side effects and safety considerations with empagliflozin?

Named safety risks in the prescribing information and medication guides include diabetic ketoacidosis and other ketoacidosis, intravascular volume depletion and symptomatic hypotension, serious urinary tract infections including urosepsis and pyelonephritis, genital mycotic infections, necrotizing fasciitis of the perineum (Fournier’s gangrene), hypoglycemia when used with insulin or insulin secretagogues (and an increased hypoglycemia risk in pediatric patients aged 10 years and older), acute kidney injury and impairment in renal function, hypersensitivity reactions (including angioedema), and signals such as increases in LDL-C and reports of lower limb amputation; the label instructs assessment of renal function and volume status before initiation and monitoring thereafter.

Dapagliflozin Cuts UACR 29·3% (DAPA-CKD); Empagliflozin: HF and CKD Indications

Dapagliflozin Cuts UACR 29·3% (DAPA-CKD); Empagliflozin: HF and CKD Indications

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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